In 1967, the present inventors, and their associators investigated the resistance mechanism of resistant bacteria against some aminoglycosidic antibiotics such as streptomycin and kanamycins which were used widely as chemotherapeutic agents towards 1967, and elucidated for the first time the resistance mechanism such that these antibiotics can be inactivated by the action of various modifying enzymes as produced by the resistant bacteria. Then, further investigations were conducted, where a variety of kanamycin derivatives which cannot be inactivated by these modifying enzymes were synthetically prepared. Some sucesses were then obtained in proving the resistance mechanism of resistant bacteria against such kanamycin derivatives and also providing such various kanamycin derivatives which are actually useful as chemotherapeutic agents for bacterial infections [see, H. Umezawa and S. Kondo: "Aminoglycoside Antibiotics" edited by H. Umezawa and I. R. Hooper, Springer-Verlag, Berlin, Heidelberg, New York, page 267 (1982); and S. Kondo: "Biochemistry of Drug Resistance Mechanism", edited by S. Mitsuhashi, published by Gakkai Publishing Center, page 27 (1981)].
Amongst these kanamycin derivatives, 3',4'-dideoxykanamycin B, i.e. dibekacin [H. Umezawa et al., "J. Antibiotics", 24, 485 (1971)] has been used widely as chemotherapeutic agent active against drug-resistant bacteria since 1975. On the other hand, (S)-1-N-(4-amino2-hydroxybutyryl)dibekacin, i.e. arbekacin [S. Kondo et al., "J. Antibiotics", 26, 412, (1973)] has been used as a specific medicine for treating infections with methicillin-resistant Staphylococcus aureus (MRSA) since the end of 1990.
In the meanwhile, there was known only one compound named seldomycin factor-5 as such an aminoglycosidic antibiotic which contains deoxystreptamine whose 2"- and 3"-positions each bear an amino group and which has the following formula (A): ##STR1## Seldomycin factor-5 is produced by Streptomyces hofunensis [J. B. McAlpine et al., "J. Antibiotics", 30, 39 (1977)], but this antibiotic compound is clearly different in its chemical structure and antibacterial activity from the new 2"-amino-2"-deoxy derivatives of dibekacin and arbekacin now provided according to this invention.
In recent years, methicillin-resistant Staphylococcus aureus (MRSA) has brought about such a serious trouble that this bacterial strain rapidly propagated through hospital infections, leading to very serious infectious diseases. Thus the development of effectively usable therapeutic agents therefor is being earnestly wanted. Arbekacin has now been used for more than one year, but there has appeared yet no arbekacin-resistant strain of MRSA (which will show a minimum growth inhibitory concentration of arbekacin of not less than 25 .mu.g/ml), in clinics. Since, however, there has been found the presence of such a strain of MRSA which exhibits a moderate resistance to arbekacin (with showing a minimum growth inhibitory concentration of arbekacin between 6.25-12.5 .mu.g/ml), we, the present inventors, have investigated detaildly the resistance mechanism of the MRSA strain having the moderate resistance to arbekacin. As a result, we have affirmed that the resistance mechanism of MRSA to arbekacin is due primarily to an enzymatic inactivation of arbekacin by phosphorylation of the 2"-OH group of arbekacin.
Based on these findings, we have further proceeded our study with the intention of synthesizing such novel derivatives of dibekacin or arbekacin which are not or little susceptible of the enzymatic phosphorylation. Thus, an object of this invention is to provide new dibekacin or arbekacin derivatives which are obtainable from dibekacin through chemical syntheses, which have broad and effective antibacterial activities not only against MRSA, but also against gram-positive and gram-negative bacteria, and which are of low toxicity.